A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Other: PlaceboBiological: Certolizumab PegolBiological: Methotrexate
- Registration Number
- NCT01519791
- Lead Sponsor
- UCB Pharma SA
- Brief Summary
This study is intended to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in combination with Methotrexate (MTX) for inducing and sustaining clinical response in the treatment of Disease Modifying Antirheumatic Drug (DMARD)-naïve adults with early active Rheumatoid Arthritis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 880
- Subjects must have a time since diagnosis of adult-onset Rheumatoid Arthritis (RA) less than 1 year as defined by the 2010 ACR/EULAR classification criteria from Screening Visit
- Positive Rheumatoid Factor (RF) and/or positive anticyclic Citrullinated Peptide Antibody (anti-CCP)
- Active RA disease
- DMARD-naïve
- Subject is naïve to RA related biologics
- A diagnosis of any other inflammatory Arthritis
- History of infected joint prosthesis, or other significant infection and other serious medical condition
- Known Tuberculosis (TB) disease or high risk of acquiring TB infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Methotrexate Placebo - Certolizumab Pegol + Methotrexate Certolizumab Pegol - Placebo + Methotrexate Methotrexate - Certolizumab Pegol + Methotrexate Methotrexate -
- Primary Outcome Measures
Name Time Method Percentage of Subjects in Sustained Remission at Week 52 Week 52 Sustained remission is defined as a Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) \< 2.6 at both Weeks 40 and 52.
DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula:
0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
- Secondary Outcome Measures
Name Time Method Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52 Week 52 Sustained LDA is defined as a Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) ≤ 3.2 at both Weeks 40 and 52.
Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52 From Baseline (Week 0) to Week 52 Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.
Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52 From Baseline (Week 0) to Week 52 Radiographic non-progression is defined as change in mTSS ≤ 0.5.
Change From Baseline in the Joint Erosion Score to Week 52 From Baseline (Week 0) to Week 52 Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.
The maximum possible erosion score for all 32-hand joints was 160. The maximum possible erosion score for all 12 feet joints was 120. Thus, the maximum possible total erosion score for hands and feet was 280.Change From Baseline in the Joint Narrowing Score to Week 52 From Baseline (Week 0) to Week 52 Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The maximum possible score for JSN in all 30 hand joints was 120. The maximum possible score for JSN in all 12 feet joints was 48. Thus, the maximum possible total JSN score for Hands and feet was 168.
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52 From Baseline (Week 0) to Week 52 The assessments are based on a 20 % or greater improvement from Baseline in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52 Week 52 LDA is defined as achieving a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) ≤ 3.2.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52 From Baseline (Week 0) to Week 52 The assessments are based on a 50 % or greater improvement from Baseline in the number of tender joints, a 50 %, or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52 From Baseline (Week 0) to Week 52 The assessments are based on a 70 % or greater improvement from Baseline in the number of tender joints, a 70 %, or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52 Week 52 The ACR/EULAR 2011 remission criteria is defined as:
Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1, C-reactive protein (CRP) ≤ 1 mg/dl and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52 Week 52 DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula:
0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice at Week 52 Week 52 The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:
Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52 From Baseline (Week 0) to Week 52 DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula:
0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28\[ESR\] change from Baseline indicates an improvement from Baseline.Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 Number of work days with reduced productivity in the last month for employed subjects.
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52 Week 52 CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52 Week 52 SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52 From Baseline (Week 0) to Week 52 Good response is defined as:
DAS28\[ESR\] ≤ 3.2 and decrease from Baseline by \> 1.2;
moderate response is defined as achievement of one of the following:
* DAS28\[ESR\] ≤ 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2
* DAS28\[ESR\] \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6
* DAS28\[ESR\] \> 5.1 and decrease from Baseline \>1.2.Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52 From Baseline (Week 0) to Week 52 CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
The CDAI score ranges from 0 to 76, with a negative value in CDAI change from Baseline indicating an improvement from Baseline.Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52 From Baseline (Week 0) to Week 52 The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.
The total score ranges from 0 (no difficulty) to 3 (unable to do) with lower scores meaning lower disability.
A negative value in HAQ-DI change from Baseline indicates an improvement from Baseline.Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52 From Baseline (Week 0) to Week 52 SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline.Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference) for employed subjects.
Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 Number of days with reduced household work productivity in the last month.
Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52 Week 52 Normative physical function is defined as HAQ-DI score ≤ 0.5. The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.
The total score ranges from 0 to 3 with lower scores meaning lower disability.Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52 From Baseline (Week 0) to Week 52 BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue).
A negative value in BRAF-MDQ change from Baseline indicates an improvement from Baseline.Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 Number of work days missed in the last month for employed subjects.
Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 Number of days with no household work in the last month.
Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 Number of days with hired outside help in the last month.
Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 Number of days missed of family/social/leisure activities in the last month.
Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 Week 52 The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).
Trial Locations
- Locations (178)
159
🇺🇸Los Angeles, California, United States
178
🇺🇸Corpus Christi, Texas, United States
223
🇺🇸Houston, Texas, United States
180
🇺🇸Mobile, Alabama, United States
75
🇸🇪Uppsala, Sweden
236
🇺🇸Durham, North Carolina, United States
170
🇺🇸Huntsville, Alabama, United States
251
🇺🇸Tucson, Arizona, United States
257
🇺🇸Hemet, California, United States
160
🇺🇸Covina, California, United States
202
🇺🇸Upland, California, United States
172
🇺🇸Whittier, California, United States
196
🇺🇸Jupiter, Florida, United States
201
🇺🇸San Leandro, California, United States
238
🇺🇸Lake Mary, Florida, United States
190
🇺🇸Fort Lauderdale, Florida, United States
232
🇺🇸Miami, Florida, United States
213
🇺🇸Naples, Florida, United States
255
🇺🇸Orlando, Florida, United States
214
🇺🇸Ocala, Florida, United States
237
🇺🇸Orange Park, Florida, United States
163
🇺🇸Palm Harbor, Florida, United States
166
🇺🇸Plantation, Florida, United States
192
🇺🇸Sarasota, Florida, United States
244
🇺🇸Springfield, Illinois, United States
200
🇺🇸Vero Beach, Florida, United States
224
🇺🇸South Bend, Indiana, United States
215
🇺🇸Cedar Rapids, Iowa, United States
177
🇺🇸Hagerstown, Maryland, United States
203
🇺🇸Tupelo, Mississippi, United States
198
🇺🇸Eagan, Minnesota, United States
179
🇺🇸Saint Louis, Missouri, United States
256
🇺🇸Reno, Nevada, United States
229
🇺🇸Lebanon, New Hampshire, United States
176
🇺🇸Brooklyn, New York, United States
207
🇺🇸Albuquerque, New Mexico, United States
242
🇺🇸Plainview, New York, United States
245
🇺🇸Middleburg Heights, Ohio, United States
195
🇺🇸Bethlehem, Pennsylvania, United States
167
🇺🇸Duncansville, Pennsylvania, United States
168
🇺🇸Wyomissing, Pennsylvania, United States
217
🇺🇸Allen, Texas, United States
162
🇺🇸Dallas, Texas, United States
185
🇺🇸Amarillo, Texas, United States
161
🇺🇸Austin, Texas, United States
206
🇺🇸Houston, Texas, United States
184
🇺🇸Houston, Texas, United States
158
🇺🇸Mesquite, Texas, United States
175
🇺🇸Nassau Bay, Texas, United States
249
🇺🇸Plano, Texas, United States
233
🇺🇸Kennewick, Washington, United States
197
🇺🇸San Antonio, Texas, United States
174
🇺🇸Glendale, Wisconsin, United States
183
🇺🇸Clarksburg, West Virginia, United States
284
🇦🇷Rosario, Argentina
291
🇦🇷Tucuman, Argentina
6
🇦🇺Coffs Harbour, New South Wales, Australia
2
🇦🇺Herson, Queensland, Australia
1
🇦🇺Maroochydore, Queensland, Australia
8
🇦🇺Woodville South, South Australia, Australia
4
🇦🇺Geelong, Victoria, Australia
5
🇦🇺Fitzroy, Victoria, Australia
3
🇦🇺Malvern, Victoria, Australia
51
🇧🇪Brussels, Belgium
36
🇧🇪Kortrijk, Belgium
126
🇧🇪Gilly, Belgium
235
🇨🇦Hamilton, Ontario, Canada
188
🇨🇦Montreal, Quebec, Canada
293
🇨🇴Bogota, Colombia
272
🇨🇴Bogota, Colombia
299
🇨🇴Bogota, Colombia
288
🇨🇴Chia, Colombia
297
🇨🇴Bucaramanga, Colombia
271
🇨🇴Medellin, Colombia
34
🇫🇷Orleans, France
124
🇨🇿Bruntal, Czechia
108
🇨🇿Brno, Czechia
38
🇨🇿Hradec Kralove, Czechia
16
🇫🇷Le Kremlin Bicetre, France
85
🇫🇷Le Mans, France
88
🇫🇷Montpellier Cedex 5, France
52
🇩🇪Bad Doberan, Germany
17
🇩🇪Bayreuth, Germany
89
🇩🇪Erfurt, Germany
113
🇩🇪Berlin, Germany
120
🇩🇪Berlin, Germany
70
🇩🇪Frankfurt, Germany
71
🇩🇪Hamburg, Germany
81
🇩🇪Hildesheim, Germany
114
🇩🇪Würzburg, Germany
132
🇩🇪Ratingen, Germany
61
🇩🇪München, Germany
127
🇩🇪Lingen, Germany
53
🇩🇪Planegg, Germany
69
🇩🇪Rheine, Germany
49
🇩🇪Rendsburg, Germany
18
🇭🇺Budapest, Hungary
131
🇭🇺Szolnok, Hungary
19
🇭🇺Veszprem, Hungary
110
🇭🇺Szombathely, Hungary
33
🇮🇪Cork, Ireland
281
🇲🇽Durango, Mexico
286
🇲🇽Guadalajara, Mexico
280
🇲🇽Monterrey, Mexico
67
🇵🇱Elblag, Poland
92
🇵🇱Poznan, Poland
100
🇵🇱Warszawa, Poland
44
🇵🇱Wroclaw, Poland
111
🇷🇴Bucharest, Romania
47
🇪🇸Madrid, Spain
63
🇪🇸Santiago de Compostela, Spain
76
🇸🇪Göteborg, Sweden
82
🇸🇪Huddinge, Sweden
106
🇸🇪Lund, Sweden
77
🇸🇪Stockholm, Sweden
118
🇨🇭Fribourg, Switzerland
125
🇬🇧Cannock, United Kingdom
105
🇬🇧Dudley, United Kingdom
56
🇬🇧Leeds, United Kingdom
121
🇬🇧London, United Kingdom
80
🇬🇧Sheffield, United Kingdom
119
🇬🇧York, United Kingdom
27
🇬🇧London, United Kingdom
191
🇺🇸Wichita, Kansas, United States
210
🇺🇸Wichita, Kansas, United States
7
🇦🇺Perth, Western Australia, Australia
279
🇦🇷San Juan, Argentina
65
🇧🇪Yvoir, Belgium
189
🇺🇸Charleston, South Carolina, United States
204
🇺🇸Hendersonville, Tennessee, United States
247
🇺🇸Glendale, Arizona, United States
165
🇺🇸Paradise Valley, Arizona, United States
298
🇨🇴Medellin, Colombia
205
🇺🇸Columbia, South Carolina, United States
181
🇺🇸Lincoln, Nebraska, United States
226
🇺🇸Coeur d'Alene, Idaho, United States
228
🇺🇸Clifton, New Jersey, United States
234
🇺🇸Paradise Valley, Arizona, United States
199
🇺🇸Kalamazoo, Michigan, United States
303
🇨🇴Barranquilla, Colombia
54
🇮🇪Dublin, Ireland
194
🇨🇦Trois-rivieres, Quebec, Canada
86
🇭🇺Eger, Hungary
22
🇷🇴Bucharest, Romania
25
🇷🇴Bucharest, Romania
26
🇷🇴Bucharest, Romania
24
🇷🇴Iasi, Romania
240
🇨🇦Kelowna, British Columbia, Canada
32
🇮🇪Limerick, Ireland
302
🇲🇽Merida, Mexico
78
🇲🇨Monaco, Monaco
128
🇵🇱Bydgoszcz, Poland
99
🇵🇱Krakow, Poland
74
🇵🇱Torun, Poland
42
🇳🇱Leiden, Netherlands
58
🇷🇴Brasov, Romania
68
🇨🇭St. Gallen, Switzerland
21
🇭🇺Budapest, Hungary
292
🇲🇽Mexico City, Mexico
294
🇲🇽San Luis Potosi, Mexico
115
🇮🇹Ferrara, Italy
122
🇮🇹Milano, Italy
40
🇮🇹Reggio Emilia, Italy
41
🇮🇹Verona, Italy
72
🇮🇹Roma, Italy
276
🇦🇷Buenos Aires, Argentina
50
🇦🇹Wien, Austria
57
🇷🇴Lasi, Romania
37
🇨🇿Praha, Czechia
79
🇫🇷Strasbourg, France
93
🇪🇸Coruna, Spain
209
🇺🇸Birmingham, Alabama, United States
241
🇺🇸Oklahoma City, Oklahoma, United States
243
🇺🇸Phoenix, Arizona, United States
186
🇺🇸Portland, Oregon, United States
123
🇸🇪Malmö, Sweden
59
🇩🇪Zerbst, Germany
227
🇺🇸Rochester, New York, United States